Oncotarget

Research Papers:

Coroglaucigenin enhances the radiosensitivity of human lung cancer cells through Nrf2/ROS pathway

Meng Sun, Dong Pan, Yaxiong Chen, Ya Li, Kun Gao and Burong Hu _

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Oncotarget. 2017; 8:32807-32820. https://doi.org/10.18632/oncotarget.16454

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Abstract

Meng Sun1, Dong Pan2,3, Yaxiong Chen2,3, Ya Li1, Kun Gao1, Burong Hu2,3

1State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China

2Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China

3Key Laboratory of Space Radiobiology of Gansu Province, Lanzhou, 730000, China

Correspondence to:

Kun Gao, email: npchem@lzu.edu.cn

Burong Hu, email: hubr@impcas.ac.cn

Keywords: coroglaucigenin, Calotropis gigantea, human lung cancer, radiosensitivity, Nrf2/ROS

Received: August 11, 2016     Accepted: March 04, 2017     Published: March 22, 2017

ABSTRACT

Seven cardenolides isolated from the ethanol extract of the stems of Calotropis gigantea were evaluated in vitro against human cancer cells and the structure-activity relationships were discussed. The results demonstrated that a compound, named CGN (coroglaucigenin), had better anti-proliferative activity with the IC50 value less than 6 μM among these compounds. Further, we found that CGN displayed much lower cytotoxicity to normal lung epithelial cells (BEAS-2B) than cancer cells (A549). Especially, our results demonstrated that treatment with CGN (1 μM) combined with X-ray irradiation induced higher radiosensitivity in human lung cancer cells (A549, NCI-H460, NCI-H446) but not in BEAS-2B. The expression levels of nuclear transcription factor Nrf2 and Nrf2-driven antioxidant molecule NQO-1 reduced in A549 cells after combined treatment compared to the radiation only. However, CGN had no toxicity and the levels of antioxidant molecules expression were higher in BEAS-2B cells when given the similar treatment as A549 cells. These results suggest that CGN is a very promising potential sensitizer for cancer radiotherapy, which not only inhibits the proliferation of cancer cells but also enhances the radiosensitivity of cancer cells through suppressing the expression of antioxidant molecules while there is no influence for normal cells.


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